The mission of the Boston University Mass Spectrometry Research Resource for Biology and Medicine is the development and application of advanced, mass spectrometry-based methods for the characterization of biopolymers that are relevant to human health and disease. Its steady progress has been fostered by close working relationships between basic scientists, clinicians and trainees at the student and postdoctoral levels. During the next grant period, the Resource will carry out Technological Research and Development (TR&D) projects that are designed to address the needs of major collaborators with whom it has identified Driving Biological Projects (DBPs) and will also use the tools and approaches that result from these efforts to solve challenging biological questions raised by additional collaborators and the wider community. The TR&D goal of the BUSM MS Resource is to advance MS methods and instrumentation to meet the short- and long-term needs of medicine. The selection of DBPs aims to identify new areas appropriate for MS in the health sciences, develop new MS-based approaches to meet the requirements of these fields and apply cutting-edge MS to the solution of critical questions in the life sciences. The Resource will focus on the needs of glycobiology for detailed structural elucidations and the profiling of complex mixtures of glycans. In particular, glycan fragmentation pathways will be thoroughly explored using novel electron-based and established dissociation methods and new bioinformatics tools will be developed for glycan analysis. Methods for 2-D analysis of glycans, lipids and proteins on surfaces and in tissues will be developed. Ion mobility mass spectrometry will be investigated for the analysis of glycans, glycoconjugates and complex peptide mixtures and for the characterization of noncovalent complexes. Top-down analysis of variant and post-translationally modified proteins will be pursued to establish relationships among PTMs on individual proteins, to provide straightforward clinical analyses, and to probe protein-glycan and protein-protein interactions. The Resource will train students, postdoctoral fellows and practicing scientists in mass spectrometry, and educate the local, national and international community about modern MS to encourage its wide and appropriate use.